The purpose of this project is to determine the role of major histocompatibility antigens in T cell responses to foreign materials. To that end, several different approaches have been taken: 1. T cell responses to non-MHC antigens, which show MHC restriction, have been selected because they give strong primary in vitro responses. The restriction of these primary responses using normal, unimmunized T cells have been examined. Thus far, such cells show MHC restriction prior to encounter with antigen. These studies are being continued. 2. T cells reactive to foreign MHC antigens have been isolated by stimulation in vitro and selection of responding cells on the basis of size. Such purified MHC-reactive T cells are then 'parked' in T cell depleted mice, and later examined for three activities: MHC-reactivity, helper activity, and non-specific suppressor activity. We plan to perform the same experiment also using antisera we are preparing to idiotypes found on T cells reacting to MHC antigens. 3. Anti-idiotypic antisera are being prepared which react with T cell receptors specific for either MHC antigens or more conventional antigens, such as the hapten DCP. By using T cell blasts responding to such antigens, we hope to be able to detect these idiotypes on T cells and, using the fluorescence-activated cell sorter, to determine how many different idiotypes each T cell can carry. Specifically, we anticipate finding one anti-MHC idiotype and one anti-conventional antigen idiotype per cell.